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Bone marrow-derived dendritic cells pulsed with a tumor-specific peptide elicit effective anti-tumor immunity against intracranial neoplasms.




 

Int J Cancer. 1998 Oct 5;78(2):196-201. Unique Identifier : AIDSLINE

Although the central nervous system (CNS) is often regarded as an immunologically privileged site, it is well established that specific CNS immunoreactivity can be generated through peripheral vaccination with CNS antigens. Dendritic cells (DC) are potent antigen presenting cells of hematopoietic origin that have emerged as a promising tool for cancer immunotherapy capable of evoking significant anti-tumor immunity when pulsed with tumor-associated peptides. To explore a role for DC-based immunization strategies for the treatment of CNS tumors, we developed a brain tumor model using the C3 sarcoma cell line which expresses the tumor-specific, major histocompatibility complex (MHC) class I-restricted peptide epitope E7(49-57). Syngeneic C57Bl/6 mice receiving intravenous (i.v.) injections of bone marrow-derived DCs pulsed with E7 peptide were effectively protected against a subsequent intracerebral challenge with C3 tumor cells. More importantly, this systemic immunization strategy was effective in a therapy model as 67% of animals (10 of 15) with established (day 7) intracerebral C3 tumors treated with 3 weekly injections of E7 peptide-pulsed DCs achieved a long-term survival (>90 days) while no control animals survived beyond day 41. In vivo depletion of CD8+ cells, but not CD4+ or asialo-GM1+ cells, abrogated the efficacy of E7 peptide-pulsed DC therapy of established tumors, indicating a pivotal role of specific CD8+ T-cell responses in mediating the anti-tumor effect. Our findings support the hypothesis that effective CNS anti-tumor immunoreactivity can be generated with DC-based tumor vaccines.

JOURNAL ARTICLE Animal Antigens, Neoplasm/IMMUNOLOGY/*THERAPEUTIC USE Bone Marrow Cells/CYTOLOGY/*IMMUNOLOGY Brain Neoplasms/IMMUNOLOGY/*PREVENTION & CONTROL CD8-Positive T-Lymphocytes/DRUG EFFECTS/IMMUNOLOGY Dendritic Cells/DRUG EFFECTS/*IMMUNOLOGY Epitopes/THERAPEUTIC USE Histocompatibility Antigens Class I/IMMUNOLOGY/THERAPEUTIC USE Immunotherapy, Adoptive/*METHODS Lymphocyte Subsets/DRUG EFFECTS/IMMUNOLOGY Mice Mice, Inbred C57BL Oligopeptides/IMMUNOLOGY/THERAPEUTIC USE



 




Information in this article was accurate in December 30, 1998. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.